MicroRNA-150 protects the mouse heart from ischaemic injury by regulating cell death

Tang, Yaoping; Wang, Yongchao; Park, Kyoung Mi; Hu, Qian-Nan; Teoh, Jian Peng; Broskova, Zuzana; Ranganathan, Punithavathi; Jayakumar, Calpurnia; Li, Jie; Su, Huabo; Tang, Yao; Ramesh, Ganesan; Kim, Il-man

doi:10.1093/cvr/cvv121

Cited by 106 publications

(133 citation statements)

References 59 publications

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“…In this study, we demonstrated for the first time that miR-150 suppresses cardiac fibrosis via c-Myb. Tang Y et al previously reported that miR-150 could repress the ischemia-induced apoptosis of cardiomyocytes by repressing the proapoptotic genes ERG2 (zinc-binding transcription factor induced by ischemia) and P2X7R (pro-inflammatory ATP receptor) [54]. The underlying mechanisms of cardiac fibrosis in different diseases are different, but there are some commonalities.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Deng

Chen

Liu

et al. 2016

Cell Physiol Biochem

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Background/Aims: Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown. Methods: We used the transverse aortic constriction (TAC) mouse model to study the role of miR-150 in cardiac fibrosis induced by pressure overload. After the TAC operation, qRT-PCR was used to measure the expression profiles of miR-150 in left ventricle tissues and populations of primary heart cell types. Then, we used both miR-150 knockout mice and wild type (WT) mice in the TAC model. Changes in cardiac function and pathology were measured using transthoracic echocardiography and pathological analysis, respectively. Furthermore, we predicted the target of miR-150 in cardiac fibroblasts (CFs) and completed in vitro CF transfection experiments using miR-150 analogs and siRNA corresponding to the predicted target. Results: We observed decreased expression levels of miR-150 in hearts suffering pressure overload, and these levels decreased more sharply in CFs than in cardiomyocytes. In addition, the degrees of cardiac function deterioration and cardiac fibrosis in miR-150-/- mice were more severe than were those in WT mice. By transfecting CFs with an miR-150 analog in vitro, we observed that miR-150 inhibited cardiac fibroblast activation. We predicted that the transcription factor c-Myb was the target of miR-150 in CFs. Transfecting CFs with c-Myb siRNA eliminated the effects of an miR-150 inhibitor, which promoted CF activation. Conclusion: These findings reveal that miR-150 acts as a pivotal regulator of pressure overload-induced cardiac fibrosis by regulating c-Myb.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Deng

Chen

Liu

et al. 2016

Cell Physiol Biochem

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“…Acute myocardial infarction was induced by permanent left-anterior descending coronary artery ligation as previously described [12, 13]. Briefly, mice were anaesthetized by using pentobarbital sodium (50 mg/kg, P3761, Sigma-Aldrich, St Louis, MO, USA) by intraperitoneal injection.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of the lncRNA Mirt1 Attenuates Acute Myocardial Infarction by Suppressing NF-κB Activation

Zhou

Huang

2017

Cell Physiol Biochem

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Background/Aims: The expression of a novel lncRNA, myocardial infarction associated transcript 1(Mirt1), has been shown to be upregulated in acute myocardial infarction (AMI). However, the role of Mirt1 in AMI is not clear. Methods: In this study, we analyzed the level of Mirt1 in cardiomyocytes and cardiac fibroblasts in AMI mice. Moreover, adenovirus mediated knockdown of Mirt1 was employed to clarify its roles in AMI mice or cultured cardiac fibroblasts. The cardiac functions and infarct size of AMI mice were examined, and tissues and cultured cells were collected and processed for histology and biochemical examination. Results: We demonstrated that Mirt1 was mainly expressed in cardiac fibroblasts, and that knockdown of Mirt1 improved cardiac functions, decreased cardiomyocytes apoptosis and attenuated inflammatory cell infiltration in vivo. Furthermore, knockdown of Mirt1 in cardiac fibroblasts not only attenuated the apoptosis of cardiomyocytes, but also suppressed the migration of macrophages under hypoxia in vitro. NF-κB signaling pathway, activated under hypoxia, was also inhibited by Mirt1 knockdown in fibroblasts. Conclusions: Knockdown of Mirt1 attenuates AMI injury presumably by decreasing cardiomyocytes apoptosis and reducing inflammatory cell infiltration. These effects could be attributed, at least partly, to inhibition of the NF-κB pathway, resulting in decreased expression of inflammatory factors.

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“…Formation of a nuclear complex of β-arrestin1 with the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and Drosha, which are crucial nuclear RNA-binding proteins involved in miR processing (Lee et al ., 2003; Guil and Caceres, 2007), leads to activation of RNA helicase-independent miR processing (Kim et al ., 2014). In the mouse hearts, 7-day carvedilol infusion induced the upregulation of miR-150, miR-214, miR-125b-5p and miR-199a-3p, which were shown to be cardioprotective in the mouse models of heart failure (Salloum et al ., 2010; Aurora et al ., 2012; Wang et al ., 2014; Tang et al ., 2015). Moreover, our group also showed that 7-day infusion of carvedilol induced a unique gene signature on multiple genes related to cardiac disease.…”

Section: Biased Signaling On Selected Gpcrsmentioning

confidence: 99%

Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology

Bologna

Teoh

Bayoumi

et al. 2017

Biomolecules & Therapeutics

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G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.

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MicroRNA-150 protects the mouse heart from ischaemic injury by regulating cell death

Abstract: These findings reveal a pivotal role for miR-150 as a regulator of cardiomyocyte survival during cardiac injury.

Cited by 106 publications

References 59 publications

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Inhibition of the lncRNA Mirt1 Attenuates Acute Myocardial Infarction by Suppressing NF-κB Activation

Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology

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